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CoCoPath Bulletin vol 1, issue 5 September/October 2015 399 Taylor Blvd, Suite 200 CoCoPathCoCoPath Bulletin Bulletin Vol 2,vol Issue 1, issue 4 5 September/October Fall2015 Pleasant Hill, CA 94523 PAPILLARYVARIAN LARCINOMAESIONS OF THEEROUS BREAST:UBAL A PATHOLOGICNTRAEPITHELIAL AND CLINICALARCINOMA, UPDATE www.cocopath.net OVARIAN CARCINOMA, SEROUS TUBAL INTRAEPITHELIAL CARCINOMA, AND THE PATHOLOGIST’S ROLE IN FALLOPIAN TUBE EXAMINATION PapillaryAND TlesionsHE ofP ATHOLOGIST’Sthe breast, despite appearROLE as INtan-pink FALLOPIAN nodules with T a UBE EXAMINATION having a common growth pattern bossellated surface or papillary Current Concepts in Pathology consistingKingINTROD Jaehae rUofyCTs onccoresIeO toNl dof m fe tbrovascularhat madness interval,confguration the rule in for a advanceddilated duct stage or tissueaKingInNdTROD g rJ eaofaetnh avariableeessrUy aCTs ronce tIweO tolengthoN sildd mes eo tfha tandhte msam athicknessden esscoi n. interval, the rule for advanced stage is a newsletter designed to keep and greatness are two sides of the same coin. cyst. Attachment to the wall by a coveredEMalignantvery tim bye a epithelium,ntumorsew Targ arisingaryen represent is binor nthe, he a diseasestalk or is sessileeventual base recurrence may both and be Current Concepts in Pathology EMalignantvery time a ntumorsew Targ arisingaryen is binor nthe, he disease is eventual recurrence and Currentour clinical Concepts colleagues in Pathology updated heterogeneoussaid, the gods toss tgroup.he coin i n Althoughthe air and t he deathobserved. from disease.Although usually less is a newsletter designed to keep our saiovary,d, the fallopian gods toss th tube,e coin iandn the peritoair and- the death from disease. is aon newsletter current topics designed in the to f eldkeep of our pathologicallywovary,orld h ofallopianlds its br eplacingat tube,h to se eand aho lesionw perito it wil inl -la nthed. than 1 cm, lesions up to 5 cm may clinical colleagues updated on “papillary”wneumorld h areolds ifrightening tcategorys breath to seis e to usuallyho w it w ilnotl la nand. clinicalpathology, colleagues and how updated they on neum areSe r frighteningBarristan Selmy ttoo D aenerys be found. Peripheral papillomas issue,contemplate—unlike difSeerentr Barris tatypesn Selmy oftcervicalo D papillaryaenerys or As HGSC often presents at a contemplate—unlikeTargaryen, Mother o fcervical Dragons or Asless HGSC often oftenpresent presents as a mass at a or with correlate with clinical practice. lesions haveTarga rdiyenf, Motherenter o fbiologic Dragons poten- relativelya nipple advanceddischarge, stage usually with are not pathology, and how they correlate endometrial- Geor gcarcinomas,e R. R. Martin, A they Storm are of relatively advanced stage with pathology, and how they correlate tial,endometrial and -morphologic Geor gcarcinomas,e R. R. Martin as, A wellthey Storm asare of grossly identifable, occur in with clinical practice. free to growSwords unchecked without widespread peritoneal involvement, with clinical practice. clinicalfree to growfeaturesSwords unchecked may overlap. without Distin - widespreadmiddle-aged peritoneal women, involvement, and may guishingproducing intraductal symptoms papilloma until they fromhave Whileproducing not symptomsquite as byzantine until they as havethe present as microcalcifcations or atypicalWhile not papilloma quite as (containingbyzantine as areas the exactmultiple site of densities origin. Traditionally, on mammography the ofpoliticsachieved atypical of a Westerosiductalrelatively hyperplasia), late succession, stage of papil the - exact site of origin. Traditionally, the politicsachieved of a Westerosirelatively late succession, stage of the siteor asof anorigin enhancing of HGSC mass has onbeen MRI. loma with ductal carcinoma in situ, site of origin of HGSC has been papillaryscreening ductal process carcinoma or minimally in situ, or Central and peripheral papillomas

invasivelymphomascreening papillary process (DLBCL) carcinomaor minimally often raises may be

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October is Breast Cancer Awareness Monthlymphomas. (THL) “triple-hit” andare ithistologically was long thought similar, that althoughthe

TES A I SSOC A GY O HOL T A P A T COS A R CONT invasive biopsy procedure available “double-hit” (DHL) and and (DHL) “double-hit” similar concerns about the patient’s and it was long thought that the

quitesimilarinvasive challenging. concerns biopsy procedure about Assessment the available patient’s of

colloquially designated as as designated colloquially majoritythe epithelial of these component cases arose ofwithin periph -

Williams and Wilkins: 2006. p. 25-46 and p. 145-157. p. and 25-46 p. 2006. Wilkins: and Williams

ued on page 2 page on ued n onti

C to assist in early diagnosis. Most of aggressive large B-cell neoplasms, neoplasms, B-cell large aggressive . D . M , l l a md Ra a h s i R myoepithelialprognosis. For cells some and time, their DLBCL distribu - ree f progression- a n i sults e r in these circumstances. circumstances. these in majority of these cases arose within

prognosis.to assist in Forearly some diagnosis. time, DLBCLMost of eral papillomas shows foci of atypi- M.D, M.D, Mandal, i n Raj

pathology. Diagnosis by needle core biopsy. 2nd edition. Philadelphia: Lippincott Lippincott Philadelphia: edition. 2nd biopsy. core needle by Diagnosis pathology.

uently q fre rapy e

toxic chemoth toxic the ovary. Primary fallopian tube

associated with HGSC is mutation is HGSC with associated tion within the lesion may be critical

nitive diagnosis for the excision specimen specimen excision the for diagnosis nitive f de defer to prudent

BCL2, and BCL6 genes has has genes BCL6 and BCL2,

. D . M , r e n t a L y r r a

B hasthese been tumors recognized are carcinomas as a of cal ductal hyperplasia and ductal - o cyt by owed l fol ction”) u

(“cytored the ovary. Primary fallopian tube 5. Rosen PP, Hoda SA. Benign papillary tumors. Papillary carcinoma. In: Breast Breast In: carcinoma. Papillary tumors. papillary Benign SA. Hoda PP, Rosen 5.

recently, evaluation of the MYC, MYC, the of evaluation recently, hasthese been tumors recognized are carcinomas as a of M.D. M.D. , g n a w H Dennis

entrapped epithelium within a reactive stroma. It thus seems seems thus It stroma. reactive a within epithelium entrapped in determining an accurate diagnosis,

tumor visible l al e v o m re to ing

HGSC

phia: W.B. Saunders/Elsevier. 2009; p. 319-350. p. 2009; Saunders/Elsevier. W.B. phia: carcinoma in situ more frequently

following standard therapy. More More therapy. standard following e J . D . M , s i t r u

C surface epithelial origin, and of

- k l debu surgical lthough A mon. m co

may not be available to assess and, when present, can contain contain can present, when and, assess to available be not may and might require immunohisto-

F M higher risk of treatment failure failure treatment of risk higher . D . M , a c s e C e n i t s i r h C

EATURES OF OF EATURES OLECULAR OLECULAR surface epithelial origin, and of

- Philadel Clinics. Pathology Surgical in pathology breast in concepts Current editor.

etastases m e

and regional lymph nod lymph regional and thethan tumor solitary, was either central restricted papillomas. to the

subtype, the latter associated with a a with associated latter the subtype,

sion can be especially treacherous since the edge of the lesion lesion the of edge the since treacherous especially be can sion . D . M , e n r y B k c i

N chemicaloutcomesthese carcinomas, analysis. following approximately T standardis review is an

s i pelv e th eyond b spread with sease, i d

4. Mulligan AM. Encapsulated papillary carcinoma of the breast. In: Collins LC LC Collins In: breast. the of carcinoma papillary Encapsulated AM. Mulligan 4. the tumor was either restricted to the

(GCB) or activated B-cell (ABC) (ABC) B-cell activated or (GCB) outcomes following standard Both are comprised of broad fbro-

i M.D. M.D. i b Shiha Nader

salpingo-oophorectomy (RRSO). salpingo-oophorectomy these carcinomas, approximately In this edition, Dr. Jefrey

IV or III e stag with present es) i stud

- inva for biopsy core a in proliferations papillary atypical ing

Williams and Wilkins; 2009 p. 205-235. p. 2009 Wilkins; and Williams attempt to provide an overview of tube, or when the fallopian tube was as either a germinal-center B-cell B-cell germinal-center a either as

: h t a P o C o

C treatment, and various approaches

in women undergoing risk-reducing risk-reducing undergoing women in three quarters fall into the category In this edition, Dr. Nicholas Byrne

e som in (90% nts e pati of ty i

major tube,vascular or when cores the with fallopian arborizing tube was

- Evaluat resection. the in DCIS nding f of the likelihood of of likelihood the of treatment, and various approaches 3. Schnitt SJ, Collins LC: Biopsy interpretation of the breast. Philadelphia: Lippincott Lippincott Philadelphia: breast. the of interpretation Biopsy LC: Collins SJ, Schnitt 3.

occurring within the fallopian tube tube fallopian the within occurring three quarters fall into the category In this edition, Dr. Nicholas Byrne

papillaryhave been breast taken lesions in attempting with an to fronds. Myoepithelial cells are Curtis discusses the classifca-

increased scrutiny of the changes changes the of scrutiny increased

ed in a core biopsy requires excisional biopsy because because biopsy excisional requires biopsy core a in ed f identi

lesions. A review of the literature. Arch Pathol Lab Med. 2016; 104: 770-787. 104: 2016; Med. Lab Pathol Arch literature. the of review A lesions. of high grade serous carcinoma eadly d most the of e n o s i HGSC . y m to c ngo-oophore i salp ng i c u red discusses our evolving under-

subcategories. Gene expression expression Gene subcategories. emphasishave been on taken diagnostic in attempting features, to

origin of HGSC, resulting from from resulting HGSC, of origin of high grade serous carcinoma disctionuss andes o histologicur evolvin featuresg unde rof-

risk f o e l ro the nd a cases, most 2. Agoumi M, Giambattistas, Hayes MM. Practical considerations in breast papillary papillary breast in considerations Practical MM. Hayes Giambattistas, M, Agoumi 2. present within the papillae and at

C S A

complicating interpretation. An atypical papillary lesion lesion papillary atypical An interpretation. complicating A NOM I ARC ERIOUS showing only minimal involvement

thinking about the putative site of of site putative the about thinking appropriate(HGSC). classifcation, prognosis,

n i a m ino c car pithelial e tra n i l ba u t

have been taken in attempting to to attempting in taken been have standing of ovarian carcinoma, its

C S showing only minimal involvement 140: 628-643. 140: : NOMA I ARC S U ERO

proliferation commonly cause fragmentation of the specimen, specimen, the of fragmentation cause commonly proliferation (HGSC). the periphery of involved spaces. stapapillarynding of breast ovarian lesions, carc inoma,as well its treatment, and various approaches approaches various and treatment,

serous n withi n i g i or tubal ve i putat andsubcategories. clinical management. Gene expression

1. Wei Shi. Papillary lesions of the breast: An update. Arch Pathol Lab Med. 2016; 2016; Med. Lab Pathol Arch update. An breast: the of lesions Papillary Shi. Wei 1.

e procedure itself as well as the papillary nature of the the of nature papillary the as well as itself procedure e T sies.

outcomes following standard standard following outcomes

ts i a, m o n i c car n a i ar v o of g n i d stan subcategories. Gene expression putative tubal origin within serous

(HGSC).

showing only minimal involvement involvement minimal only showing

References: puastat managementive tubal or iconsiderations.gin within serous - r de un ing v evol r u o iscusses d of high grade serous carcinoma carcinoma serous grade high of -

Papillary lesions account for between 1 and 4% of core biop core of 4% and 1 between for account lesions Papillary Although usually readily identif-

has been recognized as a a as recognized been has SNTRADUCTALEROUS CARCINOMA: APILLOMA three quarters fall into the category category the into fall quarters three Byrne Nicholas Dr. edition, this In undergo excision for complete evaluation of the lesion. the of evaluation complete for excision undergo I P tubal intraepithelial carcinoma in

tube, or when the fallopian tube was was tube fallopian the when or tube, EROUS ARCINOMA:

prognosis. For some time, DLBCL DLBCL time, some For prognosis. S C able, when inconspicuous they may

these carcinomas, approximately approximately carcinomas, these thinking about the putative site of tubal intraepithelial carcinoma in

the tumor was either restricted to the the to restricted either was tumor the

similar concerns about the patient’s patient’s the about concerns similar

that patients with benign papilloma on core biopsy biopsy core on papilloma benign with patients that ERIOUS ARCINOMA

B N C L P

IOPSY EEDLE ORE ON ESIONS APILLARY APILLARY thinking about the putative site of

surface epithelial origin, and of of and origin, epithelial surface A S C be highlighted by immunostaining most cases, and the role of risk

lymphoma (DLBCL) often raises raises often (DLBCL) lymphoma as eitherERIOUS a germinal-center ARCINOM B-cellA tions of available data, current recommendations are are recommendations current data, available of tions A S C

these tumors are carcinomas of of carcinomas are tumors these Intraductal papillomas may be origin of HGSC, resulting from most cases, and the role of risk

the ovary. Primary fallopian tube tube fallopian Primary ovary. the as either a germinal-center B-cell for p63 and high molecular weight CoCoPath:

to assist in early diagnosis. Most of of Most diagnosis. early in assist to origin of HGSC, resulting from

majority of these cases arose within within arose cases these of majority politics of Westerosi succession, the the succession, Westerosi of politics -

ing do not require surgical excision. Due to the limita the to Due excision. surgical require not do ing central,HGSC solitary,is one of andthe minvolveost dea largedly reducing salpingo-oophorectomy.

an indolent fashion. indolent an (GCB) or activated B-cell (ABC)

invasive biopsy procedure available available procedure biopsy invasive increased scrutiny of the changes

While not quite as byzantine as the the as byzantine as quite not While

and it was long thought that the the that thought long was it and (GCB)HGSC oris oactivatedne of the B-cellmost de (ABC)adly cytokeratins. Myoepithelial markers reducing salpingo-oophorectomy.

- imag concordant and biopsy core on papilloma benign screening process or minimally minimally or process screening Nick Byrne, M.D.

the patients, implying invasive papillary carcinoma behaves in in behaves carcinoma papillary invasive implying patients, the ducts,subtype, or peripheral,the latter associated often multiple, with a increased scrutiny of the changes

ds r o w

S occurringlike calponin within and the smooth fallopian muscle tube are some studies which argue that patients with a a with patients that argue which studies some are

site of origin of HGSC has been been has HGSC of origin of site presence of nodal metastases in approximately one-third of of one-third approximately in metastases nodal of presence of m r to S A , tin r Ma . R . R e g or e G

- andsubtype, distributed the latter within associated terminal with a achieved a relatively late stage of of stage late relatively a achieved occurring within the fallopian tube

exact site of origin. Traditionally, the the Traditionally, origin. of site exact actin may cross-react with stromal Christine Cesca, M.D. s n o g a r D f o r e h t Mo , n e y r a g ar T majority of patients (90% in some ere ere T patients and potential selection bias, however. however. bias, selection potential and patients higher risk of treatment failure

disease free survival was approximately 90% despite the the despite 90% approximately was survival free disease

producing symptoms until they have have they until symptoms producing ductolobular units. Te central

s y r e n e a D o t y m l e S n a t is r r a B r e S

highermajority risk of patof treatmentients (90% failure in som e in women undergoing risk-reducing CoCoPath:

free to grow unchecked without without unchecked grow to free fbroblasts, vascular pericytes and

0-25%. Past studies are hampered by a small number of of number small a by hampered are studies Past 0-25%. in women undergoing risk-reducing . d n la l il w t i w o h see o t h at e r b s t i s d l o h d l r o w

ovary, which can involve the breast. In one series, 5 year year 5 series, one In breast. the involve can which ovary,

widespread peritoneal involvement, involvement, peritoneal widespread CoCoPath: clinical practice. clinical

with with lesionsfollowingstudies) most pr standardes encommonlyt with therapy. stag occure III More or in I Vthe

e h t d an air e h t n i coin e h t oss t ds o g he t , d sai Jefrey Curtis, M.D.

endometrial carcinomas, they are are they carcinomas, endometrial salpingo-oophorectomy (RRSO).

relatively advanced stage with with stage advanced relatively following standard therapy. More Nader Shihabi M.D.

pathology, and how they correlate correlate they how and pathology, diagnosis of benign papilloma in a core ranges from from ranges core a in papilloma benign of diagnosis studies) present with stage III or IV endothelial cells, causing confusion. e h , n r o b is n e y r a g ar T w e n a e im t y r e v E metastatic papillary carcinoma, especially from the lung and and lung the from especially carcinoma, papillary metastatic

contemplate—unlike cervical or or cervical contemplate—unlike 30-50 year age group, arise in salpingo-oophorectomy (RRSO). Nader Shihabi M.D.

As HGSC often presents at a a at presents often HGSC As . n coi e sam e h t f o s de si o w t e r a ss e tn a e r g

and recently,disease, w evaluationith spread bofe yothend MYC, the pe lvis

biopsy to ADH, DCIS, or invasive cancer after a a after cancer invasive or DCIS, ADH, to biopsy

neum are frightening to to frightening are neum

Invasive papillary carcinoma should be distinguished from from distinguished be should carcinoma papillary Invasive Te epithelial lining may be com-

ss e n d a m t ha t me d l o t e c n o s y r e a h e a J g n

Ki NiDennisck Byrn He, wanM.Dg,. M.D.

clinical colleagues updated on on updated colleagues clinical segmentalrecently,disease, w evaluationi thor sprsub-segmentalead bofe yothend MYC, th lactifere pe lvis-

-

ovary, fallopian tube, and perito and tube, fallopian ovary, Nick Byrne, M.D. death from disease. from death is a newsletter designed to keep our our keep to designed newsletter a is

e frequency of an upgrade on excisional excisional on upgrade an of frequency e T issue. solved

cular invasion, lymph node metastases, and a poor prognosis. prognosis. poor a and metastases, node lymph invasion, cular BCL2,and reg iandona lBCL6 lymph genesnode mhasetastas es posed of a single layer of cuboidal to

Malignant tumors arising in the the in arising tumors Malignant ous ducts, and present with a nipple

Current Concepts in Pathology Pathology in Concepts Current OLECULAR EATURES OF

disease is eventual recurrence and and recurrence eventual is disease BCL2,and reg iandona lBCL6 lymph genesnode mhasetastas es M F ChBarristriyn eL Catneescra, ,M. MD.D. .

- unre somewhat a remains biopsy core via ed f identi -

surrounded by empty spaces and associated with lymphovas with associated and spaces empty by surrounded columnarOLECULAR cells orEATURES show varying OF

I Christine Cesca, M.D.

interval, the rule for advanced stage stage advanced for rule the interval,

N O I T C

NTRODU dischargecommon. whichAlthou maygh su bergi cabloody.l debu l k- M F Whether to re-excise benign intraductal papillomas papillomas intraductal benign re-excise to Whether brovascular cores cores brovascular f

lesion composed of neoplastic cells without without cells neoplastic of composed lesion Je Curtis, M.D.

Imagingcommon. commonly Although sshowsurgica la d singleebulk- HGSCdegrees of proliferation and usual Je RishaC Ruramdatis, Mll,. DM.. D. E T F R P T A aggressive large B-cell neoplasms, XAMINATION UBE ALLOPIAN IN OLE ATHOLOGIST’S HE

ND ing to remove all visible tumor HGSC

retroareolaraggressiveing to rem olarge vemass all B-cell vi insi blea dilatedneoplasms, tumor duct on ductal hyperplasia. Te degree of Dennis Hwang, M.D. C I T S , C O

ARCINOMA, ARCINOMA, NTRAEPITHELIAL UBAL EROUS ARCINOMA VARIAN colloquially(“cytoreduct idesignatedon”) follow edas by cyto- epithelial proliferation may become DennisNader H Swhihabiang, M.D., M.D .

mammography,colloquially(“cytoreduct idesignatedon”) intraluminal follow edas by c fytllingo- Barry Latner, M.D.

September/October 2015 September/October 5 issue 1, vol CoCoPath Bulletin Bulletin CoCoPath “double-hit” (DHL) and Barry Latner, M.D.

defect/ducttoxic chemoth dilatationerapy fr equenon galactogratly - associatedso pronounced with HGSC as to cause is mutation contigu- David Zlotnick, M.D.

“double-hit”toxic chemoth (DHL)erapy f randequen tly associatedous growth with between HGSC papillae,is mutation poten- Rajni Mandal, M.D, s in Pathology in s

oncept phy,“triple-hit” and a smooth-walled (THL) lymphomas. cystic Rajni Mandal, M.D,

September/October 2015 September/October results in a progression-free C Current Current “triple-hit” (THL) lymphomas. tially obscuring its papillary nature, Risha Ramdall, M.D. lesionresults or in hyperechoica progression nodule-free on Continued on page 2 Risha Ramdall, M.D. ultrasonography. Grossly they CContiontinnuedued on on page page 2 2

CONTRA COSTA PATHOLOGY ASSOCIATES 399 Taylor Blvd, Ste 200, PleasantCONT Hill, RCAA COS9452T3A | OPfAficTeHOL: 92O5-GY270-357 ASSOC5 | FIAaTESx: 925-270-3589 | www.cocopath.net 399 Taylor Blvd, Ste 200, Pleasant Hill, CA 94523 | Office: 925-270-3575 | Fax: 925-270-3589 | www.cocopath.net Current Concepts in Pathology Current Concepts in Pathology CurrentFALL Concepts in Pathology CurrentFALL Concepts in Pathology

CoCoPath Bulletin vol 1, issue 5 September/October 2015 CoCoPath Bulletin vol 1, issue 5 September/October 2015 OVARIAN CARCINOMA, SEROUS TUBAL INTRAEPITHELIAL CARCINOMA, OVARIAN CARCINOMA, SEROUS TUBAL INTRAEPITHELIAL CARCINOMA, CoCoPath Bulletin vol 1, issue 5 September/October 2015 CoCoPath Bulletin vol 1, issue 5 September/October 2015 AND THE PATHOLOGIST’S ROLE IN FALLOPIAN TUBE EXAMINATION AND THE PATHOLOGIST’S ROLE IN FALLOPIAN TUBE EXAMINATION and raising concern for atypical ADH AND DCIS IN BENIGN remain a difcult distinction 5 fold for solitary papillomas and ENCAPSULATED the fbrous capsule. For this reason, invasive foci should be clearly OductalVARIAN hyperplasia CARCINOMA or ductal carci,- SKingINEROUSITROD JNTRADUCTALaehaerUCys oncTIeO toN ldT me tUBALhat madne ssP APILLOMAS INTRAEPITHELIALinterval, the rule for advancedoutside stage the C ARCINOMA,context of a papilloma, O7 foldVARIAN for multiple CARCINOMA papillomas. , SKingINEROUSTROD(INTRACYSTIC) JaehaerUCys oncTIeO toN ldT me tUBALhat madness P APILLARYINTRAEPITHELIALinterval, the rule for advanced stage CARCINOMA, and greatness are two sides of the same coin. and greatness are two sides of the same coin. present beyond the fbrous capsule, noma in situ. Florid epithelial EMalignantvery time a ntumorsew Targ arisingaryen is binor nthe, he disease is eventual recurrenceit andshould notCurrent be Conceptssurprising in Pathology that Papillomas without atypia confer EMalignantverCy timARCINOMAe a ntumorsew Targ arisingaryen is binor nthe, he disease is eventual recurrence and Current Concepts in Pathology and staging based on the size of the AhyperplasiaND THE shows PATHOLOGIST’S syncytial or saiovary,d T, tRhe fallopian geodOLE sepithelial toss th tube,e coin IN inand the peritoair Fcomponent anALLOPIANd- the death of from an disease. TUBEseparating EXAMINATION DCISis a newsletter from designed ADH to keep in our a Aa riskND of T betweenHE PATHOLOGIST’S 1-2%, compa- saiovary,d , tRhe fallopian godOLEs toss th tube,e coin IN inand the peritoairF anALLOPIANd- the death from disease. TUBE EXAMINATIONis a newsletter designed to keep our world holds its breath to see how it will land. clinical colleagues updated on world holds its breath to see how it will land. invasive foci clinicalonly. colleagues Rare updatedpatients on streaming growth with slit-like neumotherwise are frightening benign to intraductal papilloma is controversial. Vari- rable to proliferative breast neumT areis frightening pathologic to entity consists of Ser Barristan Selmy to Daenerys As HGSC often presents at a Ser Barristan Selmy to Daenerys As HGSC often presentswith at a encapsulated papillary carci- lumina characteristic of usual contemplate—unlikepapillomaTargaryen, Mother o mayfcervical Dragons developor areas which disease without atypia. While no contemplate—unlikeTargaryen, Mother o fcervical Dragons or ous attemptspathology, at de andfning how they objective correlate a nodule (or nodules) of papillary pathology, and how they correlate Kingductal Jaeha hyperplasia.erys once told me tThate m benignadness endometrial carcinomas, they are relatively advanced stage with Kingconsensus Jaehaery sexists once tol dfor me separatingthat madness endometrial carcinomas, they are relatively advanced stage nomawith and no frankly invasive INTRODUCTION wouldinterval,- George Rraise. Rthe. Mart i nrule,concern A Stor mfor of advanced for atypical stage criteria to aidwith thisclinical distinctionpractice. have INTRODUCTION interval,carcinoma- George R. Rthe. Mart inrulesurrounded, A Stor mfor of advanced by a stage thick with clinical practice. andiagnosisd greatness a rmaye two besid escon of tfhermed same coi byn. freeductal to growSwords unchecked hyperplasia without or ductalwidespread carci peritoneal- involvement, aADHnd grea tnfromess ar eDCIS two sides in of ath epapilloma, same coin. free to growSwords unchecked without widespread peritoneal involvement,disease demonstrate distant metas- disease is eventual recurrence and beenCurrent proposed, Concepts including in Pathology arbitrary diseasefbrous is capsule eventual without recurrence evidence and Current Concepts in Pathology EMalignantvpatchy,ery time amosaic ntumorsew Tar g stainingarisingaryen is bino rfor nthe, h eCK5/6. Whileproducingnoma not symptomsquite in as situ byzantine until outside they as havethe the context of EMalignantthever ydistinction time a ntumorsew Tar isg arisinga rofye nquestionable is binor nthe, he Whileproducing not symptomsquite as byzantine until they as havethe tases and lymph node metastases, exact site of origin. Traditionally,quantitative the cutofs of 3 mm and of stromal invasion. Itexact often site of origin. Traditionally, the saiADHd, the go andds toss DCIS the coin characteristicallyin the air and the politicsachievedadeath papilloma. of a Westerosirelatively from latesuccession,disease. stage T ofe thedistinction is a newsletter designed to keep our saiclinicald, the go dsimportance, toss the coin in asthe bothair and the politicsachieveddeath of a Westerosirelatively from latesuccession,disease. stage of the lendingis a newsletter credence designed to the theory to keep that our ovary,do not fallopian express tube, this and antibody perito- (see site of origin of HGSC has30% been to distinguish ADH from ovary, fallopian tube, and perito- presents in older patientssite of with origin of a HGSC hasthis been may represent an indolent world holds its breath to see how it will land. between these entities arising in a clinical colleagues updated on wlesionsorld hold ares its bbestreath tmanagedo see how it wbyill land. nipple discharge or as a subareo- clinical colleagues updated on neumbelow). are frightening to lymphomascreening process (DLBCL) or minimally often raises DCIS within a papilloma, and a neum are frightening to lymphomascreening process (DLBCL) or minimally often raises form of invasive carcinoma. None- papilloma is not straightforward,and it was long thought that the complete excision with careful lar mass. Te neoplasmand consists it was long thought that the Ser Barristan Selmy to Daenerys similarinvasiveAs concerns biopsyHGSC procedure about often the available patient’s presents at a qualitative distinction that any Ser Barristan Selmy to Daenerys similarinvasiveAs concerns biopsyHGSC procedure about often the available patient’s presents at a theless, outcome studies show an contemplate—unlike cervical or especially in a core biopsy,majority and of these cases arose within contemplate—unlikefollow-up and evaluation cervical ofor tissue of delicate papillae coveredmajority ofby these cases arose within VaryingTarg adegreesryen, Mothe rof of Dmyoepithelialragons prognosis.to assist in Forearly some diagnosis. time, DLBCLMost of focuspathology, of monomorphic and how they cells correlate fulfll - surroundingTargaryen ,the Moth papilloma.er of Dragons Te prognosis.to assist in Forearly some diagnosis. time, DLBCLMost of excellentpathology, prognosis and how with they conserva correlate- hastheselesions relativelybeen tumors recognized are with carcinomasadvanced as a these of stage features withthe ovary. have Primary fallopian tube hasthese relativelybeenuniform tumors recognized are carcinomas advancedand as a monotonous of stage withthe ovary. Primary fallopian tube endometrialhyperplasia,- Geor gcarcinomas,e R apocrine. R. Martin, A theymetaplasia, Storm are of ing architectural and cytologic endometrialpresence- G eofor gcarcinomas, eADH R. R. Ma orrtin , DCISA they Storm are oinf the tive management and adequate local surfacebeen epithelial termed origin, and“atypical of papilloma”. with clinical practice. surfacefrequently epithelial origin, strati and of fed columnar with clinical practice. squamousSwords metaplasia, and sclerosis Whilewidespread these peritoneal neoplastic involvement, thefeatures tumor was either restrictedcriteria to the for DCIS, regardless of adjacentSw otissuerds should be the widespread peritoneal involvement,the tumor was either restrictedtherapy to the alone. freemay to begrow observed. unchecked When without the latter outcomesthese carcinomas, following approximately standard free to grow unchecked without outcomestheseepithelium carcinomas, following approximately standard displaying low to treatment,three quarters and fall various into theapproaches category tube, or when the fallopiansize, tube was be termedIn this edition,DCIS. Dr. Nicholas A WHO Byrne major feature infuencing further treatment,threeintermediate quarters and fall various into theapproaches categorygrade nucleartube, or when the fallopian tube was In this edition, Dr. Nicholas Byrne producingbecomes symptoms pronounced until the they lesion have producing symptoms until they have NVASIVE APILLARY While not quite as byzantine as the haveof high been grade taken serous in attempting carcinoma to consensus statementdiscusses our ev osuggestslving under- a 3 Whileclinical not management. quite as byzantine as the haveof highatypia. been grade taken serous in Papillary, attempting carcinoma to cribriform, and I Pdiscusses our evolving under- may be termed a sclerosing papil- exact site of origin. Traditionally,showing only the minimal involvement exact site of origin. Traditionally,showing only the minimal involvementARCINOMA politicsachieved of a Westerosirelatively late succession, stage of the (HGSC). mm cutof. stan Tdingese of ovardefiannitions carcinoma , its politicsachieved of a Westerosirelatively late succession, stage of the (HGSC).solid architecture may be seen, C standing of ovarian carcinoma, its loma and papillary features may subcategories.site of origin Gene expression of HGSC has been APILLARY subcategories.site of origin Gene expression of HGSC has been not be obvious, leading to histo- apply to lowpu tativnucleare tubal origin grade with lesionsin serous P DCIS and myoepithelial cells are not putative tubal origin within serous SEROUS CARCINOMA: tubal intraepithelial carcinoma in SEROUS CARCINOMA: Tese are unusualtubal intraepithe invasivelial c arciductalnoma i n logic overlap with ductal adenoma, thinking about the putativeonly, site of and all higher grade lesions identifed within or surroundingthinking about the putative site of screening process or minimally ERIOUS ARCINOMA screening process or minimally ERIOUS ARCINOMA carcinomas in which the infltrating lymphoma (DLBCL) often raises A S C are termed mostDCIS cases, regardless and the role of riskof lymphomaPapillary DCIS(DLBCL) involves often raisessmall A Sthe papillaryC nodules. Tis lesion most cases, and the role of risk complex sclerosing lesion, and as eitherand a it germinal-center was long B-cellthought thatorigin the of HGSC, resulting from and medium-sized ducts as deli- as eitherand a it germinal-center was long B-cellthought thatorigin the of HGSC, resultingneoplasm from consists of papillary similarinvasive concerns biopsy procedure about the available patient’s (GCB)HGSC oris oactivatedne of the B-cellmost d (ABC)eadly increased scrutiny of the changesextent. Whenredu cassessinging salpingo-oophore a monoctomy-. similarinvasive concerns biopsy procedure about the available patient’s (GCB)HGmaySC oris oactivated nebe of thae B-cellmanifestationmost d (ABC)eadly increased of a scrutinylow of the changes reducing salpingo-oophorectomy. invasive carcinoma. Myoepithelial cate fbrovascular cores covered structures of variable size composed cells remain discernible around at subtype,majority the latter of associated these withcases a aroseoccurring within within the fallopianmorphic tube low grade papillary prolif- subtype,majoritygrade the latter invasive of associated these withcancercases a arose withoccurring within an within the fallopian tube prognosis.to assist in Forearly some diagnosis. time, DLBCLMost of highermajority risk of patof treatmentients (90% failure in som e prognosis.toby assist a uniform in Forearly somepopulation diagnosis. time, DLBCLMost of of highermajority risk of patof treatmentients (90% failure in som e of malignant epithelium on fbro- least some of the entrapped pseu- in women undergoing risk-reducingeration in aC coreoCoP abiopsy,th: it is our expansile growth patternin women rather undergoing risk-reducing CoCoPath: followingstudithees) pres ovary. standardent with therapy.Primary stage III More or IVfallopian tube malignant cells, often columnar followingstudithees) pres ovary. standardent with therapy.Primary stage III More or IVfallopian tube vascular cores. A desmoplastic hasthesedoin been tumorsfltrative recognized are glandscarcinomas as a and ofepithelial salpingo-oophorectomy (RRSO).custom to diagnosisNader Shihabi M.D.“atypical hasthese been tumors recognized are carcinomas as a of than an in situ lesion, butsalpingo-oophorectomy is (RRSO). Nader Shihabi M.D. recently,disease, w evaluationith spread bofeyond the MYC, the pe lvis and of low to intermediate recently,disease, w evaluationith spread bofeyond the MYC, the pe lvis stroma and retraction around cell surfacenests epithelialburied within origin, the and sclerotic of papillary proliferation”,Nick Byrne, M.D. discuss the surface epithelial origin, and of typically treated and staged as Nick Byrne, M.D. BCL2,and reg iandona lBCL6 lymph genesnode mhasetastas es nuclear grade, oriented perpen- BCL2,and reg iandona lBCL6 lymph genesnode mhasetastas es clusters is characteristic. “Invasive stroma, and the stroma itself has a maythe tumor involve was a either papilloma restrictedM toOLECULAR varyingto the F EATURES di OFf erential Cdiagnosis,hristine Cesca, M and.D. defer theductal tumor carcinoma was either in restricted situ.MOLECULAR Con to the- F EATURES OF Christine Cesca, M.D. outcomesthese carcinomas, following approximately standard comextent,mon. Although areas surgi caofl de benignbulk- papilloma Je Curtis, M.D. outcomesthesedicular carcinomas, to following fbrovascular approximately standard stalks. It common. Although surgical debulk- papillary carcinoma”Je Curtis , isM .notD. intended more hyalinized, sclerotic appear- aggressive large B-cell neoplasms, HGSC fnal classifcation to the defnitive aggressivecurrent large B-cell DCIS neoplasms, in the adjacent HGSC ing tube,to remo vore al lwhen visible tu themor fallopian tube was Dennis Hwang, M.D. ing tube,to remo vore al lwhen visible tu themor fallopian tube was to denote encapsulatedDennis Hwang, M.D. papillary treatment,threeance quarters than and usually fall various into associated theapproaches category with colloquiallymust designatedbe identi as fable to entertain resectionIn this edition, to prevent Dr. Nicholas overtreatment Byrne treatment,threeis distinguished quarters and fall various intofrom theapproaches papilloma category colloquiallystroma designated is associated as with In this edition, Dr. Nicholas Byrne (“cytoreduction”) followed by cyto- Barry Latner, M.D. (“cytoreduction”) followed by cyto- Barry Latner, M.D. invasive tumor. Hemorrhage and “double-hit”this diagnosis. (DHL) and DCIS, whenassociated pres with HGSC- is mutation involved by DCIS because no “double-hit”increased (DHL) andrisk of recurrence.associated with Foci HGSC iscarcinoma mutation with an invasive compo- have been taken in attempting to toxic chemotherapy frequently of such lesions.Rajni Mandal, M.D, have been taken in attempting to toxic chemotherapy frequently Rajni Mandal, M.D, of high grade serous carcinoma “triple-hit”ent, is (THL) low lymphomas. grade with cribriform or discusses our evolving under- ofevidence high grade of residualserous carcinoma benign “triple-hit” (THL) lymphomas. nent.disc Inuss thees o latterur evo instance,lving unde ther- infarction, especially in large results in a progression-free resultsof in invasive a progression- fcarcinoma,ree usually showing only minimal involvement Continued on page 2 Risha Ramdall, M.D. showing only minimal involvement Continued on page 2 Risha Ramdall, M.D. (HGSC).central lesions, may occur sponta- solid architecture. Te neoplastic Tstae nclinicalding of signi ovarianfcance carc inoma,of extent its (HGSC).papilloma is identifable. Te ductal, may be seen at the invasivestand incomponentg of ovarian is carusuallycinoma, its foci are characterized by a mo- stroma within the papillae is invasive ductal carcinoma of no subcategories.neously due Gene to torsion expression of the stalk of atypia is uncertain. Some subcategories. Gene expression periphery of the nodular foci. or be trauma-associated after fne notonous uniform epithelialCONTRA COS prolifTA PATHOL- OGY ApSSOCutatIATESive tubal origin within serous delicate rather than prominent CONTRA COSTA PATHOLOGYspecial ApSSOCutatIA type,TESive tu notbal invasiveorigin w ipapillarythin serous 399 Taylor Blvd, Ste 200, Pleasant Hill, CA 94523 | Office: 925-27studies0-3575 | Fax: 9have25-270-3 found589 | www.c onocopat dih.netf erence in Tese3 9foci9 Taylor mayBlvd, Ste vary200, Ple asinant Hsizeill, CA 9and4523 | O ffice: 925-270-3575 | Fax: 925-270-3589 | www.cocopath.net SneedleEROUS aspiration CARCINOMA: or core biopsy. eration of atypical cells with round recurrencetubal intraep whenithe lesionslial carc wereinoma in SandERO fbroticUS CARC likeI NOMA:in benign intra- carcinoma.tubal intraep It alsoithe islial not car equivalentcinoma in Entrapped benign epithelium may hyperchromaticthinking about the nuclei putative displaying site of a stratifed by extent of atypia. In ductalpapillomas, and DCIS with thinkingbe confused about with the putative entrapped site of with invasive micropapillary carci- A SERIOUS CARCINOMA most cases, and the role of risk A SERIOUS CARCINOMA most cases, and the role of risk as be either observed a germinal-center at the periphery B-cell of rigidorigin architecture of HGSC, resulting and absent from patients treated with complete as various either architecturala germinal-center patterns B-cell may originneoplastic of HGSC, epithelium resulting within from noma, a biologically aggressive cellular streaming or overlapping. be found in adjacent ducts com- (GCB)HGinfarctedSC oris oactivatedne papillomas of the B-cellmost and de (ABC)a dlshowy excision,reducing recurrence salpingo-oophore rates werectomy . (GCB)HGSC oris oactivatedne of the B-cellmost de (ABC)adly CLINICAL TAKE HOME PrOeIduNTSc ing salpingo-oophorectomy. reactive atypia and/or squamous Distinguishingincreased scrutiny these of the areas changes from small, most likely due to complete monly. Cribriform, solid, and increasedIntraductal scrutinypapillomas of the changesBeni gn and adequately treated by excision. subtype,metaplasia. the latter associated with a usualoccurring ductal within hyperplasia the fallopian follow tube excision of the atypical cell popu- subtype,micropapillary the latter growth associated patterns with a occurringAtypia/DCI Swithin in papill othemas fallopian Btubeest m anaged by complete excision with careful follow-up. ADH criteria utilized outside the context may be found in ducts involved or DCIS in adjacent t ssue influences further management. highermajority risk of patof treatmentients (90% failure in som e lation confned to a localized area. highermajority risk of patof treatmentients (90% failure in som e Papillary ductal carcinoma in situ Managed as DCIS. Intraductal papillomas are benign ofin womena papilloma. undergoing Myoepithelial risk-reducing cells OtherCoC studiesoPath :have suggested a 4-5 by papillary DCIS. Myoepithe- in women undergoing risk-reducing CoCoPath: followingstudies) pr standardesent with therapy. stage III More or IV followingstudies) pr standardesent with therapy. stage III More or IV Encapsulated (intracystc) papillary May represent an indolent form of invasive carcinoma, but is and adequately treated by excision. aresalpingo-oophorectomy typically absent in (RRSO).the areas of foldNader risk Shiha of developingbi M.D. breast lial cells are not present in the salpingo-oophorectomycarcinoma (RRSO).staged as in situ carcNaderinoma (T iShihas) and trbeia teM.D.d with conservatve recently,diRisksease, ofw evaluation ithsubsequent spread bofe yo thebreastnd MYC, th ecancer pe lvis in ADH and DCIS but are present in cancer in women who had ADH recently,dipapillaesease, w evaluationbutith spr areea dnoted bofe yothend at MYC, th thee p e lvis management and adequate local therapy. Invasive foci must be patients with solitary intraductal the residual benign papilloma and inN aic papilloma,k Byrne, M .aD risk. comparable periphery of the involved spaces. present beyond the fiNbriocuks cBapysrunlee, ,a ndM s.tDag.i ng is based on the BCL2,and reg iandona lBCL6 lymph genesnode mhasetastas es BCL2,and reg iandona lBCL6 lymph genesnode mhasetastas es size of the invasive foci only. papilloma is comparable to other aroundMOLECULAR the periphery FEATURES of the OF toC fhndingristine CADHesca, Min .Dthe. adjacent Apocrine metaplasia is typically MOLECULAR FEATURES OF Christine Cesca, M.D. proliferative breast lesions without absent. Lesions of this type are Invasive papillary carcinoma Uncommon variant (not the same as invasive micropapillary common. Although surgical debulk- involvedHGSC spaces. Epithelial cells in breast.Je CSubsequenturtis, M.D. studies showed common. Although surgical debulk- HGSC carcinoma). Most caJsees behavCe uinr itnidso, leMnt .fDash.i on. aggressiveinatypia,g to rem and olargeve aisll B-cell approximatelyvisible neoplasms, tumor two the involved foci lack expression of that breast cancer risk associated aggressiveinmanagedg to rem olargeasve forall B-cell vi othersible neoplasms, t umformsor of times the relative risk compared to Dennis Hwang, M.D. Core biopsy consideratons - Benign intraductal Dennispapilloma Honw coarne gbi,o pM.D.sy: Ma nagement colloquially designated as CK5/6 and other high molecular with papillomas with atypia did colloquiallyDCIS. A dimorphicdesignated as population (“ctheytor generaleduction population.”) followed b y Multiple cyto- weight cytokeratins and show notBa rshowry La tanner ipsilateral, M.D. tendency, (“ofc ytorcellseduc withtion clear”) follow cytoplasmed by cyto in- a remains somewhat cBonatrovrye rsLialat, npearrt,c Mular.lDy if. there is “double-hit”papillomas (DHL) are associated and with uniformassociated ER with expression. HGSC is mutation but represented a generalized risk “double-hit”basal location (DHL) (globoid and cells) may associated with HGSC is mutationconcordance with imaging, but excision is currently toxic chemotherapy frequently Rajni Mandal, M.D, toxic chemotherapy frequently recommended for coRajmpletnie Mandal,evaluaton. M.D, “triple-hit”higher risk (THL) of concurrent lymphomas. and factor rather than a precursor “triple-hit”be found in (THL) up to lymphomas. 25% of cases - Atypical papillary lesion on core biopsy: Excisional biopsy to resubsequentsults in a progr carcinomaession-fre ethan single, results in a progression-free As ADH and DCISConti nareued onpart page of2 the lesion.Risha Ram Ted riskall, M factor.D. for papillo- and cause confusion with myo- Continued on pageeval 2uate for DCIS or Rinviasshioan ,Ram includdingal bl,ete Mr. eDval. uation of any solitary central papillomas. same biologic continuum and mas with atypia was found to be epithelial cells. entrapped glands that can mimic invasion.

CONTRA COSTA PATHOLOGY ASSOCIATES CONTRA COSTA PATHOLOGY ASSOCIATES 399 Taylor Blvd, Ste 200, Pleasant Hill, CA 94523 | Office: 925-270-3575 | Fax: 925-270-3589 | www.cocopath.net 399 Taylor Blvd, Ste 200, Pleasant Hill, CA 94523 | Office: 925-270-3575 | Fax: 925-270-3589 | www.cocopath.net